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study that specific function of
b
-arrestin. In this context,
b
-arrestin would
function to regulate all its other functions unrelated to the small GTPase.
This approach could provide a clearer picture of the role protein complex
formation plays in GTPase activation. Although for a specific GTPase,
b
-arrestin may interact with both the small G protein and its GEF, the con-
tribution of each interaction is presently unknown.
Identification of new
b
-arrestin interacting partners may also help defin-
ing the molecular mechanism by which
b
-arrestins regulate small GTPase
function. Different types of screens have helped find new
b
-arrestin inter-
actors that are related to small GTPases. For example, a proteomic analysis of
b
-arrestin-binding partners revealed that many GAPs can associate with
b
-arrestin.
103
Demonstration that in cells, these different GAPs can interact
with
b
-arrestins and impact GTPase activity would further contribute to our
understanding of their regulatory mechanism.
8. CONCLUSIONS
Although small GTPases are involved in almost all cellular processes,
their mode of activation remains simple and highly conserved. How 7TM
receptor stimulation activates signaling to this family of proteins remains an
intense and competitive domain of research. As most 7TM receptors only
directly couple to a few effectors, the heterotrimeric G proteins, the GRKs,
and the
b
-arrestins, the mechanisms by which they activate small G proteins
must be limited. Different reports have implicated both heterotrimeric
G proteins and
b
-arrestins as proximal effectors. Now that the latter are con-
sidered signaling molecules, we may find that they act to direct signaling to
many GTPases. The challenge for the future is to define how they do this in
a general way.
REFERENCES
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